Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts.
Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth factor beta (TGF-beta). CTGF is a member of a highly conserved family of peptides that include immediate early gene products cef10, cyr61, fisp12; a putative avian proto-oncogene, nov; and a drosophila gene, twisted gastrulation, tsg, that controls medial mesoderm induction during dorsal-ventral axis pattern formation, a process also controlled by TGF-beta related peptides (dpp, scw). In the adult mammal, CTGF functions as a downstream mediator of TGF-beta action on connective tissue cells, where it stimulates cell proliferation and extracellular matrix synthesis. CTGF does not appear to act on epithelial cells or immune cells. Because the biological actions of TGF-beta are complex and affect many different cell types, CTGF may serve as a more specific target for selective intervention in processes involving connective tissue formation during wound repair or fibrotic disorders. Northern blot and in situ hybridization studies have demonstrated that CTGF is coordinately expressed with TGF-beta in every fibrotic disorder examined to date. Agents that inhibit CTGF production or action could lead to the development of new therapeutic approaches for the control of fibrotic disorders in humans.
Grotendorst
G R
GR
Department of Cell Biology and Anatomy, University of Miami School of Medicine, FL 33136, USA. ggrotend@mednet.med.miami.edu
D000818:Animals; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens / Q000235:genetics* / Q000502:physiology*; D055514:Nephroblastoma Overexpressed Protein; D000090063:Proto-Oncogene Mas; D016212:Transforming Growth Factor beta / Q000502:physiology
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D008934:Mitogens; D055514:Nephroblastoma Overexpressed Protein; D000090063:Proto-Oncogene Mas; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor